Functional decline after major elective non-cardiac surgery: a multicentre prospective cohort study.

Self-reported postoperative functional recovery is an important patient-centred outcome that is rarely measured or considered in research and decision-making. We conducted a secondary analysis of the measurement of exercise tolerance before surgery (METS) study for associations of peri-operative variables with functional decline after major non-cardiac surgery. Patients who were at least 40 years old, had or were at risk of, coronary artery disease and who were scheduled for non-cardiac surgery were recruited. Primary outcome was a reduction in mobility, self-care or ability to conduct usual activities (EuroQol 5 dimension) from before surgery to 30 days and 1 year after surgery. A decline in at least one function was reported by 523/1309 (40%) participants at 30 days and 320/1309 (24%) participants at 1 year. Participants who reported higher pre-operative Duke Activity Status indices more often reported functional decline 30 days after surgery and less often reported functional decline 1 year after surgery. The odds ratios (95%CI) of functional decline 30 days and 1 year after surgery with moderate or severe postoperative complications were 1.46 (1.02-2.09), p = 0.037 and 1.44 (0.98-2.13), p = 0.066. Discrimination of participants who reported functional decline 30 days and 1 year after surgery were poor (c-statistic 0.61 and 0.63, respectively). In summary, one quarter of participants reported functional decline up to one postoperative year.

Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study.

BACKGROUND: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury. METHODS: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)]. RESULTS: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001]. CONCLUSIONS: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.

Using the 6-minute walk test to predict disability-free survival after major surgery.

BACKGROUND: The 6-min walk test (6MWT) is a common means of functional assessment. Its relationship to disability-free survival (DFS) is uncertain. METHODS: This sub-study of the Measurement of Exercise Tolerance for Surgery study had co-primary outcome measures: correlation of the preoperative 6MWT distance with 30 day quality of recovery (15-item quality of recovery) and 12 month WHO Disability Assessment Schedule scores. The prognostic utility of the 6MWT and other risk assessment tools for 12 month DFS was assessed with logistic regression and receiver-operating-characteristic-curve analysis. RESULTS: Of 574 patients recruited, 567 (99%) completed the 6MWT. Twelve months after surgery, 16 (2.9%) patients had died and 444 (77%) had DFS. The 6MWT correlated weakly with 30 day 15-item quality of recovery (ρ=0.14; P=0.001) and 12 month WHO Disability Assessment Schedule (ρ=-0.23; P<0.0005) scores. When the cohort was split into 6MWT distance tertiles, the adjusted odds ratio of low vs high tertiles for DFS was 3.13 [95% confidence interval (CI): 1.54-6.35]. The only independent variable predictive of DFS was the Duke Activity Status Index (DASI) score (adjusted odds ratio: 1.06; P<0.0005). The area under the receiver-operating-characteristic curve for DFS was 0.63 (95% CI: 0.57-0.70) for the 6MWT, 0.60 (95% CI: 0.53-0.67) for cardiopulmonary-exercise-testing-derived peak oxygen consumption, and 0.70 (95% CI: 0.64-0.76) for the DASI score. CONCLUSIONS: Of the risk assessment tools analysed, the DASI was the most predictive of DFS. The 6MWT was safe and comparable with cardiopulmonary exercise testing for all predictive assessments. Future research should aim to determine the optimal 6MWT distance thresholds for risk prediction.

Long-term outcomes and healthcare utilization following critical illness--a population-based study.

BACKGROUND: The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. METHODS: We conducted a retrospective cohort study of adults (age ≥ 18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥ 18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. RESULTS: Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84%) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11% and 29% at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60-19.68) for those ≥ 85 years of age compared with those aged 18-24 years. CONCLUSIONS: Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post-ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients.

Observational study of current use of selective decontamination of the digestive tract in UK critical care units.

BACKGROUND: Evidence supporting selective decontamination of the digestive tract (SDD) is reasonably strong. We set out to determine use in UK critical care units and to compare patient outcomes between units that do and those that do not use SDD. METHODS: A total of 250 UK general critical care units were surveyed. Case mix, outcomes, and lengths of stay for admissions to SDD units (with and without an i.v. component) and non-SDD units were compared using data from the Intensive Care National Audit & Research Centre Case Mix Programme database. RESULTS: A response was received from all the 250 critical care units surveyed. Of these, 13 (5.2%) reported using SDD on some or all admissions, and of these, 3 reported using an i.v. component. Data on 284,690 admissions (April 2008-March 2011) from units reporting to the ICNARC Case Mix Programme (CMP) were included in the analyses. Admissions to SDD (n=196) and non-SDD (n=9) units were a similar case mix with similar infection rates and average lengths of stay in the unit and hospital. There was no difference in risk-adjusted unit or hospital mortality. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component. CONCLUSIONS: Use of SDD in UK critical care is very low. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component, but did not translate into a difference in acute hospital mortality or length of stay. There is a need to better understand the barriers to adoption of SDD into clinical practice and such work is underway.

Economic evaluation of nurse-led intensive care follow-up programmes compared with standard care: the PRaCTICaL trial.

OBJECTIVE: Following intensive care discharge, many patients suffer severe physical and psychological morbidity and a continuing high use of health services. Follow-up programmes have been proposed to improve the outcomes for these patients. We tested the hypothesis that nurse-led intensive care follow-up programmes are cost-effective. METHODS: A pragmatic, multicentre, randomised controlled trial of nurse-led intensive care unit follow-up programmes versus standard care. A cost-utility analysis was conducted after 12 months' follow-up to compare the two interventions. Costs were assessed from the perspective of the UK NHS and outcomes were measured in quality-adjusted life years (QALYs) based upon responses to the EQ-5D administered at baseline, 6 and 12 months. RESULTS: A total of 286 patients were recruited to the trial. Total mean cost was £ 5,789 for standard care and £ 7,577 for the discharge clinic. The adjusted difference in means was £ 2,435 [95 % confidence interval (CI) -297 to 5,566]. Mean QALYs were 0.58 for standard care and 0.60 for the discharge clinic. The adjusted mean difference was -0.003 (95 % CI -0.066 to 0.060). If society were willing to pay £ 20,000 per QALY then there would be a 93 % chance that standard care would be considered most efficient. CONCLUSIONS: A nurse-led intensive care unit (ICU) follow-up programme showed no evidence of being cost-effective at 12 months. Further work should focus on evidence-based development of discharge clinic services and current ICU follow-up programmes should review their practice in light of these results.

Are educational interventions to prevent catheter-related bloodstream infections in intensive care unit cost-effective?

BACKGROUND: There is increasing interest in evidence-based educational interventions in central venous catheter care. It is unclear how effective these are at reducing the risk of bloodstream infections from the use of intravascular catheters (catheter-BSIs) and the associated costs and health benefits. AIM: To estimate the additional costs and health benefits from introducing such interventions and the costs associated with catheter-BSIs. METHODS: A comprehensive epidemiological and economic review was performed to develop the parameters for an economic model to assess the cost-effectiveness of introducing an educational intervention compared with clinical practice without the intervention. The model follows the clinical pathway of cohorts of patients from their admission to an intensive care unit (ICU), where some may acquire catheter-BSI, and estimates the associated costs, mortality and life expectancy. FINDINGS: The additional cost per catheter-BSI episode was £3940. The results of this model demonstrate that introducing an additional educational intervention to prevent catheter-BSI improved patient life expectancy and reduced overall costs. CONCLUSION: Introducing evidence-based education is likely to reduce the incidence of catheter-BSI and the model results suggest that the cost of introducing the interventions will be outweighed by savings related to reduced ICU bed occupancy costs.

N-terminal pro-B-type natriuretic peptide concentrations and long-term outcome after cardiac surgery: a prospective cohort study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict cardiovascular outcome in many settings. There are very few data assessing the utility of NT-proBNP concentrations in the prediction of long-term outcome after cardiac surgery. We assessed the ability of NT-proBNP to predict 3 yr mortality compared with validated clinical risk prediction tools. METHODS: A secondary analysis of a prospectively recruited patient cohort of 1010 patients undergoing cardiac surgery. Baseline clinical details were obtained including EuroSCORE. Multi-variable modelling, area under the receiver operating characteristic curves (AUCs), and net reclassification improvement were utilized. RESULTS: NT-proBNP was a univariable predictor of 3 yr mortality but was no longer a significant predictor in a multivariable model (hazard ratio 1.00 per 250 ng litre(-1), 95% confidence interval 0.98-1.02, P=0.80). The relative and additive predictive values of the preoperative EuroSCORE (both additive and logistic versions) and NT-proBNP concentrations were compared. All were predictive of 3 yr mortality (P<0.001) with almost identical AUCs (0.71 for EuroSCORE, 0.70 for NT-proBNP). When either the EuroSCORE or NT-proBNP concentrations are known, the addition of the other does not improve the ability to predict 3 yr mortality. CONCLUSIONS: Preoperative NT-proBNP concentrations and the EuroSCORE have equivalent, and moderate, predictive accuracy for mortality 3 yr after cardiac surgery. EuroSCORE uses clinical data but is not routinely used for individual clinical risk prediction. NT-proBNP measurement would incur additional costs but can be measured quickly and objectively. With such similar predictive accuracy, factors such as the ease of calculation and cost will likely determine their use in clinical practice.

The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients.

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre-operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high-risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides.

Time course of organ failure in patients with septic shock treated with hydrocortisone: results of the Corticus study.

INTRODUCTION: Corticosteroids have been proposed to decrease morbidity and mortality in patients with septic shock. An impact on morbidity should be anticipated to be earlier and more easily detected than the impact on mortality. METHODS: Prospective, randomized, double-blind, placebo-controlled study of 28-day mortality in patients with septic shock for <72 h who underwent a short high-dose ACTH test in 52 centers in 9 European countries. Patients received 11-day treatment with hydrocortisone or placebo. Organ dysfunction/failure was quantified by the use of the sequential organ failure assessment (SOFA) score. RESULTS: From March 2002 to November 2005, 499 patients were enrolled (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at baseline (hydrocortisone 10.8 ± 3.2 vs. placebo 10.7 ± 3.1 points). There was no difference in 28-day mortality between the two treatment groups (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo-treated patients (p = 0.0027), driven by an improvement in cardiovascular organ dysfunction/failure (p = 0.0005) and in liver failure (p < 0.0001) in the hydrocortisone-treated patients. CONCLUSION: Patients randomized to treatment with hydrocortisone demonstrated a faster decrease in total organ dysfunction/failure determined by the SOFA score, primarily driven by a faster improvement in cardiovascular organ dysfunction/failure. This organ dysfunction/failure improvement was not accompanied by a decreased mortality.

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

BACKGROUND: Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. METHODS: Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). RESULTS: There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. CONCLUSIONS: Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. TRIAL REGISTRATION NUMBER: The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

The use of combined physiological parameters in the early recognition of the deteriorating acute medical patient.

BACKGROUND: Early warning scores (EWS) are widely used to allow early recognition of the deteriorating patient. We aimed to test their ability to predict major deterioration in medical patients. METHODS: Two cohorts were prospectively identified who were admitted to an acute medical admissions unit and to the respiratory unit but not admitted to the intensive care unit (ICU): medical-non ICU and respiratory-non ICU groups. Two further cohorts were retrospectively identified that required ICU admission from these units (medical-ICU and respiratory-ICU groups). Discriminant analysis and receiver operating characteristic curves were used to discriminate between groups, and time relationships were analysed. RESULTS: Heart rate (HR) and respiratory rate (RR) were significantly higher--and oxygen saturation (SaO2) significantly lower--in the medical-ICU group as compared with the medical non-ICU group, and in the respiratory-ICU group as compared with [corrected] the respiratory-non ICU group. Discriminant functions incorporating HR, RR and SaO2 performed at least as well as existing EWS systems in predicting ICU admission. CONCLUSIONS: Commonly used physiological parameters and existing EWS systems are useful at identifying sick patients. The discriminant functions described here appear to have a role in this setting but require validation in future studies.

A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study).

BACKGROUND: Hospital acquired infections are a major cause of morbidity and mortality and markedly increased health care costs. Critically ill patients who require management in an Intensive Care Unit are particularly susceptible to these infections which are associated with a very high mortality. Selective decontamination of the digestive tract (SDD) may reduce these infections and improve mortality but it has not been widely adopted into practice. We aim to 1. Clarify reasons why clinicians have avoided implementing SDD into clinical practice despite the current best-evidence 2. Describe barriers to SDD implementation and 3. Identify what further evidence is required before full scale clinical implementation would be considered appropriate and feasible. METHODS: We have developed an international 'multi-lens' approach to investigate SDD from several perspectives. In case studies we will identify accounts of implementation of SDD in practice, in terms of the behaviours performed by the full range of individual clinicians, accounts of how SDD was first introduced into the Unit and specific content that may be used to populate the content of behaviour change techniques to be used in an implementation intervention and procedures to consider in order to deliver an implementation trial. In a 4 round Delphi study we will identify the range of stakeholders' beliefs, views and perceived barriers relating to the use of SDD. We will generate hypotheses about key beliefs about SDD and will inform the feasibility of any future randomised controlled trial. In large-scale nationwide postal questionnaire surveys of the state of current practice we will identify the factors predicting acceptability of an effectiveness or implementation trial using, and informed by, the theoretical domains structure. In semi-structured interviews with active international clinical trialists we will assess the feasibility of a randomised controlled trial and identify challenges and barriers to undertaking research in the field of SDD research. DISCUSSION: We believe these methods will allow us to determine whether clinical implementation trials or further large effectiveness trials are required before full scale implementation into clinical practice.

Effectiveness and cost-effectiveness of arthroscopic lavage in the treatment of osteoarthritis of the knee: a mixed methods study of the feasibility of conducting a surgical placebo-controlled trial (the KORAL study).

OBJECTIVES: To ascertain the acceptability of a randomised controlled trial comparing arthroscopic lavage with a placebo-surgical procedure for the management of osteoarthritis of the knee; and to assess the practical feasibility of mounting such a multicentre placebo-controlled trial. DESIGN: Mixed methods study including: focus groups with surgeons and anaesthetists; focus groups and interviews with potential participants; interviews with chairpersons of UK Multicentre Research Ethics Committees (MRECs); surveys of surgeons and anaesthetists; and a two-centre, three-arm pilot. SETTING: UK secondary care. PARTICIPANTS: Members of the British Association of Surgeons of the Knee and members of the British Society of Orthopaedic Anaesthetists took part in the focus groups and surveys. Surgeons and anaesthetists from two regional centres in the UK also contributed to focus groups, as did patients from consultant lists in two UK regional centres, and members of Arthritis Care. Chairpersons of six UK MRECs were interviewed. Participants were eligible for the pilot if they were adults (18 years or older) with radiological evidence of osteoarthritis of the knee who might be considered for arthroscopic lavage, and were fit for general anaesthetic (defined by the American Society of Anaesthesiologists grades 1 and 2), and able to give informed consent. INTERVENTIONS: Participants in the pilot study were randomised to arthrosocopic lavage (with or without debridement at the clinical discretion of the surgeon); placebo surgery; or non-operative management with specialist reassessment. MAIN OUTCOME MEASURES: The acceptability and feasibility of mounting a placebo-controlled trial for the evaluation of knee arthroscopic lavage. RESULTS: There was broad acceptance across all stakeholder groups of the need to find out more about the effectiveness of arthroscopic lavage. Despite this there was variation in opinion within all the groups about how researchers should approach this and whether or not it would be acceptable to investigate using placebo surgery. Within the health professional groups, there tended to be a split between those who were strongly opposed to the inclusion of a placebo surgery arm and those who were more in favour. For prospective trial participants who had osteoarthritis of the knee, the acceptability of the trial was discussed from a more individual perspective - reflecting on their personal reasons for or against participating. The majority of this group said they would consider taking part. The pilot study showed that, in principle, a placebo-controlled trial could be conducted. It showed that patients were willing to participate in a trial which would involve a placebo-surgical arm and that it was possible to undertake placebo surgery successfully and to blind patients to their allocation - although once patients knew their allocation, some patients allocated to surgery became more concerned about the possibility of undergoing placebo surgery, and withdrew. The experience of the pilot, however, showed that, despite full MREC approval, the study required major discussion and negotiation before local clinical approvals could be obtained. The fact that ethics approval had been granted did not mean that clinicians would automatically accept that the process was ethical. CONCLUSIONS: The study showed that, in principle, a placebo-controlled trial of arthroscopic lavage could be conducted in the UK, albeit with difficulty. Against the background of falling use of arthroscopic lavage the decision was, therefore, taken not to proceed to full-scale trial for this procedure. The study showed that for some health professionals the use of placebo surgery can never be justified. It highlighted the importance of the surgeon-anaesthetist relationship in this context and how acceptance of the trial design by both parties is essential to successful participation. It also highlighted the importance of informed consent for trial participants and the strength and influence of individuals' ethical perspectives in addition to collective ethics provided by MRECs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02328576.

The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial.

OBJECTIVES: To test the hypothesis that nurse led follow-up programmes are effective and cost effective in improving quality of life after discharge from intensive care. DESIGN: A pragmatic, non-blinded, multicentre, randomised controlled trial. SETTING: Three UK hospitals (two teaching hospitals and one district general hospital). PARTICIPANTS: 286 patients aged >or=18 years were recruited after discharge from intensive care between September 2006 and October 2007. INTERVENTION: Nurse led intensive care follow-up programmes versus standard care. Main outcome measure(s) Health related quality of life (measured with the SF-36 questionnaire) at 12 months after randomisation. A cost effectiveness analysis was also performed. RESULTS: 286 patients were recruited and 192 completed one year follow-up. At 12 months, there was no evidence of a difference in the SF-36 physical component score (mean 42.0 (SD 10.6) v 40.8 (SD 11.9), effect size 1.1 (95% CI -1.9 to 4.2), P=0.46) or the SF-36 mental component score (effect size 0.4 (-3.0 to 3.7), P=0.83). There were no statistically significant differences in secondary outcomes or subgroup analyses. Follow-up programmes were significantly more costly than standard care and are unlikely to be considered cost effective. CONCLUSIONS: A nurse led intensive care follow-up programme showed no evidence of being effective or cost effective in improving patients' quality of life in the year after discharge from intensive care. Further work should focus on the roles of early physical rehabilitation, delirium, cognitive dysfunction, and relatives in recovery from critical illness. Intensive care units should review their follow-up programmes in light of these results. TRIAL REGISTRATION: ISRCTN 24294750.

N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a powerful predictor of cardiovascular outcome in many circumstances. There are, however, limited data regarding the utility of NT-proBNP or BNP levels in patients undergoing cardiac surgery. The current study assesses the ability of NT-proBNP to predict early outcome in this setting. METHODS: One thousand and ten patients undergoing non-emergent cardiac surgery were recruited prospectively. Baseline clinical details were obtained and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Parsonnet score were calculated. Preoperative NT-proBNP levels were measured using the Roche Elecsys assay. The primary endpoint was 30 day mortality. RESULTS: Median NT-proBNP levels were 624 ng litre(-1) among patients who died within 30 days of surgery (n=29), compared with 279 ng litre(-1) in survivors [odds ratio (OR) 1.03 per 250 ng litre(-1), 95% confidence interval 1.01-1.05, P=0.001). NT-proBNP levels remained predictors of 30 day mortality in models including either the additive EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.01), the logistic EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.004), or the Parsonnet score (OR 1.02 per 250 ng litre(-1), P=0.04). Levels of NT-proBNP were also predictors of prolonged (>1 day) stay in the intensive care unit (OR 1.03 per 250 ng litre(-1), P<0.001) and of a hospital stay >1 week (OR 1.07 per 250 ng litre(-1), P<0.001). They remained predictive of these outcomes in regression models that included either the EuroSCORE or the Parsonnet score and in a model that included all study variables. CONCLUSIONS: NT-proBNP levels predict early outcome after cardiac surgery. Their prognostic utility is modest-but is independent of traditional indicators and conventional risk prediction scores.

Activated protein C for the treatment of severe sepsis.

In 2001, the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial demonstrated a 6.1% absolute decrease in mortality in patients with severe sepsis. Recombinant human activated protein C was subsequently licensed for use by both the US Food and Drug Administration and the European Medicines Evaluation Agency. There has been some controversy over aspects of the original study protocol, and subsequent trials have raised concerns about both the efficacy and the side effect profile of recombinant human activated protein C. Significant doubt remains as to the role of recombinant human activated protein C in the management of severe sepsis, and this review aims to summarize the evidence both for and against its use.